Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation Clinical Trial

— TREAT  

Official title:

Effect of Roflumilast 500 μg Tablets Once Daily at Acute COPD Exacerbations Treated With Standard Therapy of Oral Steroids and Antibiotics. A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01473758
• Other study ID #: RO-2455-405-RD
• Secondary ID: 2011-002905-31U1
• Status: Terminated
• Phase: Phase 2
• First received: October 31, 2011
• Last updated: February 20, 2015
• Start date: February 2012
• Est. completion date: March 2014

Study information

• Verified date: February 2015
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to investigate if roflumilast can reduce the neutrophilic inflammation at acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). In addition, the potential benefit of roflumilast on severity and recovery periods of acute COPD exacerbations will be assessed using patient diaries and questionnaires.

Description:

Participants will be asked whether they agree to participate in the measurements of arterial stiffness. Participants who agree will be included in the substudy, with the target of 60 patients with arterial stiffness measurements to complete the trial.

Study was terminated due to difficulty in identifying further eligible patients for this exploratory study within a reasonable time.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 95
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent (IC)

• Age = 40 years

• History of COPD for at least 12 months prior to enrollment (Visit V0)

• Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment

• Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour

• Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) < 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months)

• Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years

Main Exclusion Criteria:

• Diagnosis of asthma and/or other relevant lung disease

• Known alpha-1-antitrypsin deficiency

• Recurrent exacerbations (within 8 weeks of a preceding exacerbation)

• Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment

• Treatment with PDE4 inhibitors within 3 months prior to Visit V0

• Other protocol-defined exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Roflumilast
500 µg tablet, od, oral administration in the morning after breakfast
• Placebo
tablet, od, oral administration in the morning after breakfast

Locations

Country	Name	City	State
United Kingdom	Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha	London

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in sputum neutrophil counts [cells/g sputum] from Day 1 to Day 14 post exacerbation	Assessment will be done at Day 14 after randomisation	Day 1 to Day 14	No
Secondary	Change in sputum inflammatory markers	Change for the following sputum inflammatory markers: total and differential cell counts (absolute [cells/g sputum] and percentage [%]); neutrophils (except for change addressed in primary outcome); macrophages; eosinophils; lymphocytes; Sputum concentrations of interleukin (IL)-6, IL-8, myeloperoxidase (MPO), neutrophil elastase.; Proportion of patients whose sputum neutrophil counts have returned to stable state levels at Day 14 post exacerbation.	Day 1 to Day 7, Day 14, Day 28, Day 56	No
Secondary	Change in blood biomarkers	Change for the blood concentration of the following biomarkers: • C-reactive protein (CRP); • fibrinogen; • IL-6 and IL-1ß; • glucose	Day 1 to Day 7, Day 14, Day 28, Day 56	No
Secondary	Change in pulmonary function	Change for the following spirometry measurements: • Forced expiratory volume in the first second (FEV1); • forced vital capacity (FVC); • FEV1/FVC	Day 1 to Day 7, Day 14, Day 28, Day 56	No
Secondary	Diary outcomes	Diary outcomes will include the following: outcomes with respect to exacerbations; time course on a daily basis and changes on a weekly basis for PEF, respiratory symptoms and hours spent out of house	During treatment and follow-up period (up to 56 days)	No
Secondary	Patient-reported outcomes	Time course on a daily basis and changes on a weekly basis for the following: • COPD Assessment Test (CAT); • EXAcerbations of Chronic pulmonary disease Test-Patient-Reported Outcome (EXACT-PRO) questionnaire.	During treatment and follow-up period (up to 56 days)	No
Secondary	Change from Baseline in aortic pulse wave velocity in a subset of participants	Carotid-femoral aortic pulse wave velocity (aPWV) will be measured in a subset of participants to determine changes in arterial stiffness.	Baseline and Days 14 and 28.	No